It’s not news that some viruses, including human papillomavirus, human immunodeficiency virus, Epstein-Barr, and hepatitis B, can cause or accelerate the development of cancer. But a recent story in The Washington Post about rare cancers being diagnosed in individuals who had previously been infected by the coronavirus has raised the specter of whether acute respiratory syndrome coronavirus (SARS–CoV-2) could also be an instigator in the initiation of cancer.1
Although the devastating short-term severe impact of SARS–CoV-2 is evidenced by the more than 7,000,000 reported coronavirus-related deaths worldwide since the outbreak of COVID-19 was declared a pandemic by the World Health Organization, in 2020,2 the long-term implications on health are just starting to be investigated.
Afshin Beheshti, PhD
According to Afshin Beheshti, PhD, President of the COVID-19 International Research Team and Professor of Surgery and Computational and Systems Biology, Director of the Space Biomedicine Program, and Associate Director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, it is hypothesized that SARS–CoV-2 may have long-term, life-threatening complications, including the acceleration of cancer, but these cancer-related effects may take several years to manifest. In this interview with The ASCO Post, Dr. Beheshti discussed how SARS–CoV-2could be a risk factor in cancer development.
Mechanisms of COVID That May Lead to Cancer Development
Reports are starting to emerge about a possible link between the coronavirus and the acceleration of the development of cancers. Is severe SARS–CoV-2 an oncogenic agent? Could the virus be implicated in causing cancer?
All we have right now is preliminary and indirect evidence of a potential causal link between SARS–CoV-2 and cancer. When there is an injury to the body or an infection, there may be short-term cancer-related signals that go up, but they dissipate quickly. What we are seeing in some patients with long COVID is that these cancer-related signals, such as inflammatory factors and mitochondrial dysfunction, are persistent. This makes us hypothesize that SARS–CoV-2 may be an oncogenic type of virus. But if so, we don’t know whether it is an initiator of cancer or a driver of cancer progression.
There is a good study in preprint showing a connection between respiratory viral infections and the awakening of dormant metastatic breast cancer cells in the lungs.3 In this study, the researchers infected mice with SARS–CoV-2 or the influenza virus to understand the mechanisms that disrupt the quiescence of dormant disseminated cancer cells that may lead to metastatic progression. What they found is that both the influenza virus and SARS–CoV-2 increased breast disseminated cancer cell expansion in the lungs after infection. When the researchers expanded their findings to human observational data, they observed that cancer survivors who had contracted SARS–CoV-2 infection had a substantially increased risk of lung metastatic progression and cancer-related death compared with cancer survivors who had not developed SARS–CoV-2.3
So, in a sense, maybe SARS–CoV-2 creates a different landscape in the lungs, in this case, to make the cancer more susceptible to progress or for the dormant cells to become active. My colleague, Kashyap Patel, MD, Chief Executive Officer of Carolina Blood and Cancer Care Associates, is seeing rare and lethal cancers popping up in his patients after they have contracted the coronavirus, so he has a strong suspicion—but no hard evidence—that there is a link between the virus and the development of cancer.1 We are working together to figure out whether the virus is causing dormant tumors to become reactivated, or it is causing an initiation. We want to bring attention to this issue before it’s too late.
Lingering Coronavirus Fragments and Long-Term Immune Responses
Is it possible that the coronavirus, rather than disappearing from the body after it infects an individual, lingers, potentially initiating cancer?
That is one of the concerns in patients who have had long COVID infection. So far, we have not seen the virus replicating in the body 15 or 20 days after infection. But researchers studying the impact of long COVID on the body have found that fragments of SARS–CoV-2 left behind after infection may continue to trigger immune responses.4 Whether that triggers cancer mechanisms is a hypothesis we should look into.
Focusing Research on SARS–CoV-2 and the Risk for Cancer Development
What are you learning about how COVID, especially long COVID, impacts the body in terms of prematurely aging tissue? Could that process spark the development of cancer?
We don’t know the answers to those questions. Emerging evidence has pointed to mitochondrial dysfunction or mitochondria suppression as a potential underpinning mechanism contributing to the persistence of long-COVID symptoms.5 That could mean there is a long-term impact on how cells transform energy.
In cancer development, malignant cells produce energy in a unique way that supports their rapid growth and spread. Known as the Warburg effect, this process could potentially play a role in the increased risk of cancer in patients with long COVID, because their cells may experience changes that make it easier for cancer to develop and thrive.
There is also long-lasting immune activation present in patients with long COVID, which can go on for 2 to 3 years after active infection. We know that consistent upper respiratory inflammation in the body can cause cancer progression.
A lot of the research underway now in long COVID is not yet focused on cancer development and the potential for SARS–CoV-2 to cause cancer, but it’s a question researchers should investigate.
DISCLOSURE: Dr. Beheshti is on the advisory board for Tevogen Bio.
REFERENCES
1. Cha AE: ‘Unusual’ cancers emerged after the pandemic. Doctors ask if covid is to blame. The Washington Post, June 6, 2024.
2. Worldometer: Coronavirus Death Toll. Available at www.worldometers.info/coronavirus/coronavirus-death-toll. Accessed November 18, 2024.
3. Chia SB, Johnson BJ, Hu J, et al: Respiratory viral infection promotes the awakening and outgrowth of dormant metastatic breast cancer cells in lungs. Res Sq [Preprint] rs.3.rs-4210090, 2024.
4. Doctrow B: SARS–CoV-2 fragments may cause problems after infection. National Institutes of Health, February 27, 2024. Available at www.nih.gov/news-events/nih-research-matters/sars-cov-2-fragments-may-cause-problems-after-infection. Accessed November 18, 2024.
5. Molnar T, Lehoczki A, Fekete M, et al: Mitochondrial dysfunction in long COVID: Mechanisms, consequences, and potential therapeutic approaches. GeroScience 46:5267-5286, 2024.
